METHOD: Based on a pre-registered protocol (PROSPERO: CRD42022328485), we searched PubMed, Web of Knowledge/Science, Ovid Medline, Embase and APA PsycINFO up to 5th February 2022, with no language/type of document restrictions. We included observational studies 1) reporting at least one measure of vision in people of any age with a diagnosis of ASD based on DSM or ICD criteria, or ADOS; or 2) reporting the prevalence of ASD in people with and without vision disorders. Study quality was assessed with the Appraisal tool for Cross-Sectional Studies (AXIS). Random-effects meta-analyses were used for data synthesis.
RESULTS: We included 49 studies in the narrative synthesis and 46 studies in the meta-analyses (15,629,159 individuals distributed across multiple different measures). We found meta-analytic evidence of increased prevalence of strabismus (OR = 4.72 [95% CI: 4.60, 4.85]) in people with versus those without ASD (non-significant heterogeneity: Q = 1.0545, p = 0.7881). We also found evidence of increased accommodation deficits (Hedge's g = 0.68 [CI: 0.28, 1.08]) (non-significant heterogeneity: Q = 6.9331, p = 0.0741), reduced peripheral vision (-0.82 [CI: -1.32, -0.33]) (non-significant heterogeneity: Q = 4.8075, p = 0.4398), reduced stereoacuity (0.73 [CI: -1.14, -0.31]) (non-significant heterogeneity: Q = 0.8974, p = 0.3435), increased color discrimination difficulties (0.69 [CI: 0.27,1.10]) (non-significant heterogeneity: Q = 9.9928, p = 0.1890), reduced contrast sensitivity (0.45 [CI: -0.60, -0.30]) (non-significant heterogeneity: Q = 9.9928, p = 0.1890) and increased retinal thickness (=0.29 [CI: 0.07, 0.51]) (non-significant heterogeneity: Q = 0.8113, p = 0.9918) in ASD.
DISCUSSION: ASD is associated with some self-reported and objectively measured functional vision problems, and structural alterations of the eye, even though we observed several methodological limitations in the individual studies included in our meta-analyses. Further research should clarify the causal relationship, if any, between ASD and problems of vision during early life.
PROSPERO REGISTRATION: CRD42022328485.
METHOD: Based on a pre-registered protocol (PROSPERO: CRD42021256352), we searched PubMed, Web of Knowledge/Science, Ovid Medline, Embase and APA PsycINFO up to 16th November 2021, with no language/type of document restrictions. We included observational studies reporting at least one measure of vision in people of any age meeting DSM/ICD criteria for ADHD and in people without ADHD; or the prevalence of ADHD in people with and without vision disorders. Study quality was assessed with the Appraisal tool for Cross-Sectional Studies (AXIS). Random effects meta-analyses were used for data synthesis.
RESULTS: We included 42 studies in the narrative synthesis and 35 studies in the meta-analyses (3,250,905 participants). We found meta-analytic evidence of increased risk of astigmatism (OR = 1.79 [CI: 1.50, 2.14]), hyperopia and hypermetropia (OR = 1.79 [CI: 1.66, 1.94]), strabismus (OR = 1.93 [CI: 1.75, 2.12]), unspecified vision problems (OR = 1.94 [CI: 1.38, 2.73]) and reduced near point of convergence (OR = 5.02 [CI: 1.78, 14.11]); increased lag (Hedge's g = 0.63 [CI: 0.30, 0.96]) and variability (Hedge's g = 0.40 [CI: 0.17, 0.64]) of the accommodative response; and increased self-reported vision problems (Hedge's g = 0.63 [CI: 0.44, 0.82]) in people with ADHD compared to those without ADHD (with no significant heterogeneity). We also found meta-analytic evidence of no differences between people with and without ADHD on retinal nerve fiber layer thickness (Hedge's g = -0.19 [CI: -0.41, 0.02]) and refractive error (Hedge's g = 0.08 [CI: -0.26, 0.42]) (with no significant heterogeneity).
DISCUSSION: ADHD is associated with some self-reported and objectively ascertained functional vision problems, but not with structural alterations of the eye. Further studies should clarify the causal relationship, if any, between ADHD and problems of vision.
TRIAL REGISTRATION: PROSPERO registration: CRD42021256352.
AREAS COVERED: We first discuss the definition of biomarkers and the necessary research steps from discovery to implementation. We then provide a broad overview of research studies on candidate diagnostic biomarkers in ADHD encompassing genetic/epigenetic, biochemical, neuroimaging, neurophysiological and neuropsychological techniques. Finally, we critically appraise current limitations in the field and suggest possible ways forward.
EXPERT OPINION: Despite the large number of studies and variety of techniques used, no promising biomarkers have been identified so far. Clinical and biological heterogeneity as well as methodological limitations, including small sample size, lack of standardization, confounding factors, and poor replicability, have hampered progress in the field. Going forward, increased international collaborative efforts are warranted to support larger and more robustly designed studies, develop multimodal datasets to combine biomarkers and improve diagnostic accuracy, and ensure reproducibility and meaningful clinical translation.